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Early Versus Delayed Decompression For Traumatic Cervical Spinal Cord Injury: Results Of The Surgical Timing In Acute Spinal Cord Injury Study (Stascis)., Michael G Fehlings, Alex R. Vaccaro, Jefferson R Wilson, Anoushka Singh, David W Cadotte, James Harrop, Bizhan Aarabi, Christopher Shaffrey, Marcel Dvorak, Charles Fisher, Paul Arnold, Eric M Massicotte, Stephen Lewis, Raja Rampersaud

Department of Orthopaedic Surgery Faculty Papers

BACKGROUND: There is convincing preclinical evidence that early decompression in the setting of spinal cord injury (SCI) improves neurologic outcomes. However, the effect of early surgical decompression in patients with acute SCI remains uncertain. Our objective was to evaluate the relative effectiveness of early (injury) versus late (≥ 24 hours after injury) decompressive surgery after traumatic cervical SCI.

METHODS: We performed a multicenter, international, prospective cohort study (Surgical Timing In Acute Spinal Cord Injury Study: STASCIS) in adults aged 16-80 with cervical SCI. Enrolment occurred between 2002 and 2009 at 6 North American centers. The primary outcome was ordinal change …

Nutrition, Inflammation, And Infectious Disease, Helieh S. Oz, Sung-Ling Yeh

Physiology Faculty Publications

No abstract provided.

Pegylated Arginine Deiminase Downregulates Colitis In Murine Models, Helieh S. Oz, Jian Zhong, Willem J. S. De Villiers

Physiology Faculty Publications

Arginine deiminase (ADI), an arginine-metabolizing enzyme involved in cell signaling, is dysregulated in multiple inflammatory diseases and cancers. We hypothesized that pegylated ADI (ADI-PEG) provide protection against colitis.

METHODS: Dextran sodium sulfate colitis was induced in IL-10-deficient and BALB/c (WT) mice. ADI-PEG was administered i.p., and inflammatory mediators and pathology were evaluated.

RESULTS: Acute colitis in mice was manifested by increases in inflammatory biomarkers, such as serum amyloid A (SAA, P < 0.001), IL-12 p40, and disease index (3-Fold). In contrast, ADI-PEG significantly decreased clinical disease index, SAA levels, and inflammatory cytokines in blood as well as in colonic explants. Animals developed moderate (2.2 ± 0.3 WT) to severe (3.6 ± 0.5 IL-10 deficient) colonic pathology; and ADI-PEG treatment significantly improved the severity of colitis (P < 0.05). Marked infiltration of CD68+ macrophages and iNOS expression were detected in colonic submucosa in colitic animals but not detected in ADI-PEG-treated animals.

CONCLUSION: ADI-PEG attenuated inflammatory responses by suppression of macrophage infiltration and iNOS expression in colitic animals. ADI-PEG can serve as a potential therapeutic value in IBD.

The Formin Fmnl3 Is A Cytoskeletal Regulator Of Angiogenesis, Clare Hetheridge, Alice N. Scott, Rajeeb K. Swain, John W. Copeland, Henry N. Higgs

Dartmouth Scholarship

The process of angiogenesis requires endothelial cells (ECs) to undergo profound changes in shape and polarity. Although this must involve remodelling of the EC cytoskeleton, little is known about this process or the proteins that control it. We used a co-culture assay of angiogenesis to examine the cytoskeleton of ECs actively undergoing angiogenic morphogenesis. We found that elongation of ECs during angiogenesis is accompanied by stabilisation of microtubules and their alignment into parallel arrays directed at the growing tip. In other systems, similar microtubule alignments are mediated by the formin family of cytoskeletal regulators. We screened a library of human …

Rituximab Therapy In Pulmonary Alveolar Proteinosis Improves Alveolar Macrophage Lipid Homeostasis., Anagha Malur, Mani Kavuru, Irene Marshall, Barbara P Barna, Isham Huizar, Reema Karnekar, Mary Jane Thomassen

Division of Pulmonary, Allergy, and Critical Care Medicine Faculty Papers

RATIONALE: Pulmonary Alveolar Proteinosis (PAP) patients exhibit an acquired deficiency of biologically active granulocyte-macrophage colony stimulating factor (GM-CSF) attributable to GM-CSF specific autoantibodies. PAP alveolar macrophages are foamy, lipid-filled cells with impaired surfactant clearance and markedly reduced expression of the transcription factor peroxisome proliferator-activated receptor gamma (PPARγ) and the PPARγ-regulated ATP binding cassette (ABC) lipid transporter, ABCG1. An open label proof of concept Phase II clinical trial was conducted in PAP patients using rituximab, a chimeric murine-human monoclonal antibody directed against B lymphocyte specific antigen CD20. Rituximab treatment decreased anti-GM-CSF antibody levels in bronchoalveolar lavage (BAL) fluid, and 7/9 patients …

Schistosome-Derived Omega-1 Drives Th2 Polarization By Suppressing Protein Synthesis Following Internalization By The Mannose Receptor, Bart Everts, Leonie Hussaarts, Nicole N. Driessen, Moniek H.J. Meevissen, Gabriele Schramm, Alwin J. Van Der Ham, Barbara Van Der Hoeven, Thomas Scholzen, Sven Burgdorf, Markus Mohrs, Edward J. Pearce, Cornelis H. Hokke, Helmut Haas, Hermelijn H. Smits, Maria Yazdanbakhsh

Open Access Publications

Omega-1, a glycosylated T2 ribonuclease (RNase) secreted by Schistosoma mansoni eggs and abundantly present in soluble egg antigen, has recently been shown to condition dendritic cells (DCs) to prime Th2 responses. However, the molecular mechanisms underlying this effect remain unknown. We show in this study by site-directed mutagenesis of omega-1 that both the glycosylation and the RNase activity are essential to condition DCs for Th2 polarization. Mechanistically, we demonstrate that omega-1 is bound and internalized via its glycans by the mannose receptor (MR) and subsequently impairs protein synthesis by degrading both ribosomal and messenger RNA. These experiments reveal an unrecognized …

Testosterone Treatment Fails To Accelerate Disease In A Transgenic Mouse Model Of Spinal And Bulbar Muscular Atrophy., Erica S Chevalier-Larsen, Diane E Merry

Department of Biochemistry and Molecular Biology Faculty Papers

Evidence from multiple animal models demonstrates that testosterone plays a crucial role in the progression of symptoms in spinal and bulbar muscular atrophy (SBMA), a condition that results in neurodegeneration and muscle atrophy in affected men. Mice bearing a transgene encoding a human androgen receptor (AR) that contains a stretch of 112 glutamines (expanded polyglutamine tract; AR112Q mice) reproduce several aspects of the human disease. We treated transgenic male AR112Q mice with testosterone for 6 months. Surprisingly, testosterone treatment of AR112Q males did not exacerbate the disease. Although transgenic AR112Q males exhibited functional deficits when compared with non-transgenics, long-term testosterone …

Two Maximal Isometric Contractions Attenuate The Magnitude Of Eccentric Exercise-Induced Muscle Damage, Hsin-Lian Chen, Kazunori Nosaka, Alan Pearce, Trevor C Chen

Research outputs 2012

This study investigated whether maximal voluntary isometric contractions (MVC-ISO) would attenuate the magnitude of eccentric exercise-induced muscle damage. Young untrained men were placed into one of the two experimental groups or one control group (n = 13 per group). Subjects in the experimental groups performed either two or 10 MVC-ISO of the elbow flexors at a long muscle length (20° flexion) 2 days prior to 30 maximal isokinetic eccentric contractions of the elbow flexors. Subjects in the control group performed the eccentric contractions without MVC-ISO. No significant changes in maximal voluntary concentric contraction peak torque, peak torque angle, range of …

Comparative Genomics Of Brachyspira Pilosicoli Strains: Genome Rearrangements, Reductions And Correlation Of Genetic Compliment With Phenotypic Diversity, Luke Mappley, Michael Black, Manal Abuoun, Alistair C. Darby, Martin J. Woodward, Julian Parkhill, A. Keith Turner, Matthew I. Bellgard, Tom La, Nyree D. Phillips, Roberto M. La Ragione, David J. Hampson

Research outputs 2012

Background: The anaerobic spirochaete Brachyspira pilosicoli causes enteric disease in avian, porcine and human hosts, amongst others. To date, the only available genome sequence of B. pilosicoli is that of strain 95/1000, a porcine isolate. In the first intra-species genome comparison within the Brachyspira genus, we report the whole genome sequence of B. pilosicoli B2904, an avian isolate, the incomplete genome sequence of B. pilosicoli WesB, a human isolate, and the comparisons with B. pilosicoli 95/1000. We also draw on incomplete genome sequences from three other Brachyspira species. Finally we report the first application of the high-throughput Biolog phenotype screening …

Olfactory Discrimination Predicts Cognitive Decline Among Community-Dwelling Older Adults, Hamid Sohrabi, Kristyn Bates, Mg Weinborn, A N Johnston, A Bahramian, Kevin Taddei, Simon Laws, Mark Rodrigues, Michael Morici, Matthew Howard, Georgia Martins, A Mackay-Sim, Se Gandy, Ralph Martins

Research outputs 2012

The presence of olfactory dysfunction in individuals at higher risk of Alzheimer's disease has significant diagnostic and screening implications for preventive and ameliorative drug trials. Olfactory threshold, discrimination and identification can be reliably recorded in the early stages of neurodegenerative diseases. The current study has examined the ability of various olfactory functions in predicting cognitive decline in a community-dwelling sample. A group of 308 participants, aged 46-86 years old, were recruited for this study. After 3 years of follow-up, participants were divided into cognitively declined and non-declined groups based on their performance on a neuropsychological battery. Assessment of olfactory functions …

The Dermatan Sulfate Proteoglycan Decorin Modulates Α2Β1 Integrin And The Vimentin Intermediate Filament System During Collagen Synthesis., Oliver Jungmann, Katerina Nikolovska, Christian Stock, Jan-Niklas Schulz, Beate Eckes, Christoph Riethmüller, Rick T Owens, Renato V Iozzo, Daniela G Seidler

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin, a small leucine-rich proteoglycan harboring a dermatan sulfate chain at its N-terminus, is involved in regulating matrix organization and cell signaling. Loss of the dermatan sulfate of decorin leads to an Ehlers-Danlos syndrome characterized by delayed wound healing. Decorin-null (Dcn(-/-)) mice display a phenotype similar to that of EDS patients. The fibrillar collagen phenotype of Dcn(-/-) mice could be rescued in vitro by decorin but not with decorin lacking the glycosaminoglycan chain. We utilized a 3D cell culture model to investigate the impact of the altered extracellular matrix on Dcn(-/-) fibroblasts. Using 2D gel electrophoresis followed by mass spectrometry, …

Decorin Protein Core Affects The Global Gene Expression Profile Of The Tumor Microenvironment In A Triple-Negative Orthotopic Breast Carcinoma Xenograft Model., Simone Buraschi, Thomas Neill, Rick T Owens, Leonardo A Iniguez, George Purkins, Rajanikanth Vadigepalli, Barry Evans, Liliana Schaefer, Stephen C Peiper, Zi-Xuan Wang, Renato V Iozzo

Department of Pathology, Anatomy, and Cell Biology Faculty Papers

Decorin, a member of the small leucine-rich proteoglycan gene family, exists and functions wholly within the tumor microenvironment to suppress tumorigenesis by directly targeting and antagonizing multiple receptor tyrosine kinases, such as the EGFR and Met. This leads to potent and sustained signal attenuation, growth arrest, and angiostasis. We thus sought to evaluate the tumoricidal benefits of systemic decorin on a triple-negative orthotopic breast carcinoma xenograft model. To this end, we employed a novel high-density mixed expression array capable of differentiating and simultaneously measuring gene signatures of both Mus musculus (stromal) and Homo sapiens (epithelial) tissue origins. We found that …

Differential Expression Of Metabolic Genes In Tumor And Stromal Components Of Primary And Metastatic Loci In Pancreatic Adenocarcinoma., Nina V. Chaika, Fang Yu, Vinee Purohit, Kamiya Mehla, Audrey J. Lazenby, Dominick J. Dimaio, Judy M. Anderson, Jen Jen Yeh, Keith R. Johnson, Michael A. Hollingsworth, Pankaj K. Singh

Journal Articles: Eppley Institute

BACKGROUND: Pancreatic cancer is the fourth leading cause of cancer related deaths in the United States with a five-year survival rate of 6%. It is characterized by extremely aggressive tumor growth rate and high incidence of metastasis. One of the most common and profound biochemical phenotypes of animal and human cancer cells is their ability to metabolize glucose at high rates, even under aerobic conditions. However, the contribution of metabolic interrelationships between tumor cells and cells of the surrounding microenvironment to the progression of cancer is not well understood. We evaluated differential expression of metabolic genes and, hence, metabolic pathways …

High Metabolic Potential May Contribute To The Success Of St131 Uropathogenic Escherichia Coli., Tarek M. Gibreel, Andrew R. Dodgson, John Cheesbrough, Frederick J. Bolton, Andrew J. Fox, Mathew Upton

School of Biomedical Sciences

Uropathogenic Escherichia coli (UPEC) is the predominant cause of urinary tract infection in both hospital and community settings. The recent emergence of multidrug-resistant clones like the O25b:H4-ST131 lineage represents a significant threat to health, and numerous studies have explored the virulence potential of these organisms. Members of the ST131 clone have been described as having variable carriage of key virulence factors, and it has been suggested that additional unidentified factors contribute to virulence. Here we demonstrated that ST131 isolates have high metabolic potential and biochemical profiles that distinguish them from isolates of many other sequence types (STs). A collection of …

Osteochondral Tissue Engineering: Scaffolds, Stem Cells And Applications., Patcharakamon Nooeaid, Vehid Salih, Justus P. Beier, Aldo R. Boccaccini

Peninsula Dental School

Osteochondral tissue engineering has shown an increasing development to provide suitable strategies for the regeneration of damaged cartilage and underlying subchondral bone tissue. For reasons of the limitation in the capacity of articular cartilage to self-repair, it is essential to develop approaches based on suitable scaffolds made of appropriate engineered biomaterials. The combination of biodegradable polymers and bioactive ceramics in a variety of composite structures is promising in this area, whereby the fabrication methods, associated cells and signalling factors determine the success of the strategies. The objective of this review is to present and discuss approaches being proposed in osteochondral …

Cellular Retrograde Cardiomyoplasty And Relaxin Therapy For Postischemic Myocardial Repair In A Rat Model, Gabriella Di Lascio, Guy Harmelin, Mattia Targetti, Cristina Nanni, Giacomo Bianchi, Tommaso Gasbarri, Sandro Gelsomino, Daniele Bani, Sandra Zecchi Orlandini, Massimo Bonacchi

The Texas Heart Institute Journal

We sought to determine whether skeletal myoblasts, wild-type or engineered to express relaxin, might improve myocardial viability and performance in a rat model of chronic myocardial infarction. Our purpose was to investigate a potential new therapy for heart failure.

From October 2005 through September 2009, we surgically induced acute myocardial infarction in 80 male Wistar rats. Thirty days after surgery, the rats underwent reoperation for the retrograde coronary venous infusion of skeletal myoblasts, relaxin, or both. The animals were randomly assigned to 4 experimental groups: R1 (the control group, which underwent saline-solution infusion), R2 (systemic relaxin therapy), R3 (myoblast infusion), …

Does The Expression Of Transforming Growth Factor Β-1: Affect The Outcome Of The Radiofrequency Modified Maze Procedure In Patients With Rheumatic Atrial Fibrillation?, Wei Wang, Lei Liu, Yuan Li, Sheng-Shou Hu, Yun-Hu Song, Xin Wang

The Texas Heart Institute Journal

We investigated whether the expression of transforming growth factor β-1 in the left atrial appendage affected the outcome of the radiofrequency modified maze procedure in patients with rheumatic valve disease and long-standing persistent atrial fibrillation.

Messenger RNA and protein expression of transforming growth factor β-1 and volume fractions of collagen types I and III were measured in 80 patients with rheumatic valve atrial fibrillation who underwent valve surgery with the radiofrequency modified maze procedure; the same was done in a control group of 20 patients with rheumatic valve disease and sinus rhythm who underwent valve surgery alone.

At 6 months' …

Peripartum Cardiomyopathy: A Review, Anirban Bhattacharyya, Sukhdeep Singh Basra, Priyanka Sen, Biswajit Kar

The Texas Heart Institute Journal

Peripartum cardiomyopathy is idiopathic heart failure occurring in the absence of any determinable heart disease during the last month of pregnancy or the first 5 months postpartum. The incidence varies worldwide but is high in developing nations; the cause of the disease might be a combination of environmental and genetic factors. Diagnostic echocardiographic criteria include left ventricular ejection fraction2.7 cm/m(2). Electrocardiography, magnetic resonance imaging, endomyocardial biopsy, and cardiac catheterization aid in the diagnosis and management of peripartum cardiomyopathy. Cardiac protein assays can also be useful, as suggested by reports of high levels of NT-proBNP, cardiac troponin, tumor necrosis factor-α, interleukin-6, …

Cd2ap Regulates Sumoylation Of Cin85 In Podocytes, Irini Tossidou, Rainer Niedenthal, Malte Klaus, Beina Teng, Kirstin Worthmann, Benjamin King, Kevin Peterson

Dartmouth Scholarship

Podocytes are highly differentiated and polarized epithelial cells located on the visceral side of the glomerulus. They form an indispensable component of the glomerular filter, the slit diaphragm, formed by several transmembrane proteins and adaptor molecules. Disruption of the slit diaphragm can lead to massive proteinuria and nephrotic syndrome in mice and humans. CD2AP is an adaptor protein that is important for the maintenance of the slit diaphragm. Together with its paralogue, CIN85, CD2AP belongs to a family of adaptor proteins that are primarily described as being involved in endocytosis and downregulation of receptor tyrosine kinase activity. We have shown …

A Shared Gene Expression Signature In Mouse Models Of Ebv-Associated And Non-Ebv-Associated Burkitt Lymphoma, Kathryn T. Bieging, Kamonwan Fish, Subbarao Bondada, Richard Longnecker

Microbiology, Immunology, and Molecular Genetics Faculty Publications

The link between EBV infection and Burkitt lymphoma (BL) is strong, but the mechanism underlying that link has been elusive. We have developed a mouse model for EBV-associated BL in which LMP2A, an EBV latency protein, and MYC are expressed in B cells. Our model has demonstrated the ability of LMP2A to accelerate tumor onset, increase spleen size, and bypass p53 inactivation. Here we describe the results of total gene expression analysis of tumor and pretumor B cells from our transgenic mouse model. Although we see many phenotypic differences and changes in gene expression in pretumor B cells, the transcriptional …

Effects Of Prenatal Food And Micronutrient Supplementation On Child Growth From Birth To 54 Months Of Age: A Randomized Trial In Bangladesh, Ashraful Islam Khan, Iqbal Kabir, Eva-Charlotte Ekström, Kajsa Åsling-Monemi, Dewan Shamsul Alam, Edward A. Frongillo Jr., Md Yunus, Shams Arifeen, Lars-Åke Persson

Faculty Publications

Background: There is a lack of information on the optimal timing of food supplementation to malnourished pregnant women and possible combined effects of food and multiple micronutrient supplementations (MMS) on their offspring's growth. We evaluated the effects of prenatal food and micronutrient interventions on postnatal child growth. The hypothesis was that prenatal MMS and early invitation to food supplementation would increase physical growth in the offspring during 0-54 months and a combination of these interventions would further improve these outcomes.

Methods: In the large, randomized MINIMat trial (Maternal and Infant Nutrition Interventions in Matlab), Bangladesh, 4436 pregnant women were enrolled …

Histone Deacetylase Inhibitor Valproic Acid Suppresses The Growth And Increases The Androgen Responsiveness Of Prostate Cancer Cells., Yu-Wei Chou, Nagendra K. Chaturvedi, Shougiang Ouyang, Fen-Fen Lin, Dharam Kaushik, Jue Wang, Isaac Kim, Ming-Fong Lin

Journal Articles: Biochemistry & Molecular Biology

We identified the molecular target by histone deacetylase (HDAC) inhibitors for exploring their potential prostate cancer (PCa) therapy. Upon HDAC inhibitors-treatment, LNCaP cell growth was suppressed, correlating with increased cellular prostatic acid phosphatase (cPAcP) expression, an authentic protein tyrosine phosphatase. In those cells, ErbB-2 was dephosphorylated, histone H3/H4 acetylation and methylation increased and cyclin proteins decreased. In PAcP shRNA-transfected C-81 cells, valproic acid (VPA) efficacy of growth suppression was diminished. Further, VPA pre-treatment enhanced androgen responsiveness of C-81, C4-2 and MDA PCa2b-AI cells. Thus, cPAcP expression is involved in growth suppression by HDAC inhibitors in PCa cells, and VPA pre-treatments …

Widespread Regulation Of Mirna Biogenesis At The Dicer Step By The Cold-Inducible Rna-Binding Protein, Rbm3, Julie Pilotte, Esther E. Dupont-Versteegden, Peter W. Vanderklish

Physical Therapy Faculty Publications

MicroRNAs (miRNAs) play critical roles in diverse cellular events through their effects on translation. Emerging data suggest that modulation of miRNA biogenesis at post-transcriptional steps by RNA-binding proteins is a key point of regulatory control over the expression of some miRNAs and the cellular processes they influence. However, the extent and conditions under which the miRNA pathway is amenable to regulation at posttranscriptional steps are poorly understood. Here we show that RBM3, a cold-inducible, developmentally regulated RNA-binding protein and putative protooncogene, is an essential regulator of miRNA biogenesis. Utilizing miRNA array, Northern blot, and PCR methods, we observed that over …

B1b Lymphocyte-Derived Antibodies Control Borrelia Hermsii Independent Of Fcα/Μ Receptor And In The Absence Of Host Cell Contact., Matthew J. Colombo, David Abraham, Akira Shibuya, Kishore R. Alugupalli

Department of Microbiology and Immunology Faculty Papers

The critical role of IgM in controlling pathogen burden has been demonstrated in a variety of infection models. In the murine model of Borrelia hermsii infection, IgM is necessary and sufficient for the rapid clearance of bacteremia. Convalescent, but not naïve, B1b cells generate a specific IgM response against B. hermsii, but the mechanism of IgM-mediated protection is unknown. Here, we show that neither Fcα/μR, a high-affinity receptor for IgM, nor IgM-dependent complement activation is required for controlling B. hermsii. Bacteria in diffusion chambers with a pore size impermeable to cells were killed when diffusion chambers were implanted into either …

Planning Combinatorial Disulfide Cross-Links For Protein Fold Determination, Fei Xiong, Alan M Friedman, Chris Bailey-Kellogg

Dartmouth Scholarship

Fold recognition techniques take advantage of the limited number of overall structural organizations, and have become increasingly effective at identifying the fold of a given target sequence. However, in the absence of sufficient sequence identity, it remains difficult for fold recognition methods to always select the correct model. While a native-like model is often among a pool of highly ranked models, it is not necessarily the highest-ranked one, and the model rankings depend sensitively on the scoring function used. Structure elucidation methods can then be employed to decide among the models based on relatively rapid biochemical/biophysical experiments.

Development Of A New Curriculum In A Positive Youth Development Program: The Project P.A.T.H.S. In Hong Kong, Daniel T. L. Shek, Hing Keung Ma, Rachel C. F. Sun

Pediatrics Faculty Publications

The design of a new curriculum in a positive youth development program (Project P.A.T.H.S.) in Hong Kong is outlined. The Tier 1 Program of the original phase of the Project P.A.T.H.S. is a universal positive youth development program for students in Secondary 1 to Secondary 3 with the curricula developed by a research team comprising scholars in different disciplines (e.g., social work, psychology, and education). The 120 teaching units are designed with reference to 15 positive youth development constructs identified in the successful positive youth development programs. In the extension phase of the project, a new curriculum with 60 teaching …

Nanoparticulate Formulations Of Mithramycin Analogs For Enhanced Cytotoxicity, Daniel Scott, Jürgen Rohr, Younsoo Bae

Pharmaceutical Sciences Faculty Publications

Mithramycin (MTM), a natural product of soil bacteria from the Streptomyces genus, displays potent anticancer activity but has been limited clinically by severe side effects and toxicities. Engineering of the MTM biosynthetic pathway has produced the 3-side-chain-modified analogs MTM SK (SK) and MTM SDK (SDK), which have exhibited increased anticancer activity and improved therapeutic index. However, these analogs still suffer from low bioavailability, short plasma retention time, and low tumor accumulation. In an effort to aid with these shortcomings, two nanoparticulate formulations, poly(ethylene glycol)-poly(aspartate hydrazide) self-assembled and cross-linked micelles, were investigated with regard to the ability to load and pH …

An Engineered Approach To Stem Cell Culture: Automating The Decision Process For Real-Time Adaptive Subculture Of Stem Cells, Dai Fei Elmer Ker, Lee E. Weiss, Silvina N. Junkers, Mei Chen, Zhaozheng Yin, Mike F. Sandbothe, Seungil Huh, Sungeun Eom, Ryoma Bise, Elvira Osuna-Highley, Takeo Kanade, Phil Gordon Campbell

Computer Science Faculty Research & Creative Works

Current cell culture practices are dependent upon human operators and remain laborious and highly subjective, resulting in large variations and inconsistent outcomes, especially when using visual assessments of cell confluency to determine the appropriate time to subculture cells. Although efforts to automate cell culture with robotic systems are underway, the majority of such systems still require human intervention to determine when to subculture. Thus, it is necessary to accurately and objectively determine the appropriate time for cell passaging. Optimal stem cell culturing that maintains cell pluripotency while maximizing cell yields will be especially important for efficient, cost-effective stem cell-based therapies. …

Innate And Adaptive Immunity To The Nematode Strongyloides Stercoralis In A Mouse Model., Sandra Bonne-Annee, Jessica A. Hess, David Abraham

Department of Microbiology and Immunology Faculty Papers

Mice have been used to the study the mechanisms of protective innate and adaptive immunity to larval Strongyloides stercoralis. During primary infection, neutrophils and eosinophils are attracted by parasite components and kill the larvae by release of granule products. Eosinophils also function as antigen-presenting cells for the induction of a Th2 response. B cells produce both IgM and IgG that collaborate with neutrophils to kill worms in the adaptive immune response. Vaccine studies have identified a recombinant diagnostic antigen that induced high levels of immunity to infection with S. stercoralis in mice. These studies demonstrate that there are redundancies in …

Erect Wing Facilitates Context-Dependent Wnt/Wingless Signaling By Recruiting The Cell-Specific Armadillo-Tcf Adaptor Earthbound To Chromatin, Nan Xin, Hassina Benchabane, Ai Tian, Kerrie Nguyen, Lindsay Klofas, Yashi Ahmed

Dartmouth Scholarship

During metazoan development, the Wnt/Wingless signal transduction pathway is activated repetitively to direct cell proliferation, fate specification, differentiation and apoptosis. Distinct outcomes are elicited by Wnt stimulation in different cellular contexts; however, mechanisms that confer context specificity to Wnt signaling responses remain largely unknown. Starting with an unbiased forward genetic screen in Drosophila, we recently uncovered a novel mechanism by which the cell-specific co-factor Earthbound 1 (Ebd1), and its human homolog jerky, promote interaction between the Wnt pathway transcriptional co-activators B-catenin/Armadillo and TCF to facilitate context-dependent Wnt signaling responses. Here, through the same genetic screen, we find an unanticipated requirement …